This study is a multicenter clinical trial to determine if postoperative subconjunctival injections of 5-fluorouracil (5-FU) increase the success rate of filtering surgery in patients with poor prognoses. It is estimated that 344 patients with medically uncontrolled glaucoma, 214 after previous cataract extraction and 130 after previous failed filtering surgery, will be needed to satisfy the statistical demands of the study. In order to obtain these patients it is estimated that a total of 415 patients (all Centers), 258 after previous cataract extraction and 157 after previous failed filtering surgery, must be screened and offered enrollment in the study. Following trabeculectomy, patients will be randomized to either standard surgical treatment alone or standard surgery with adjunctive 5-FU. The 5-FU group will receive subconjunctival injections of 5 mg of 5-FU twice daily on postoperative days 1-7 and once daily on postoperative days 8-14. All patients will be examined one month, three months, six months, and one year following surgery. For randomization and analysis, patients will be stratified into four groups: (1) aphakic younger than 50 years of age; (2) aphakic 50 years of age or older; (3) phakic with one unsuccessful filtering procedure; (4) phakic with two or more unsuccessful filtering procedures. Success and failure rates will be calculated on the basis of defined intraocular pressure levels. Intraocular pressure determinations will be made in a standardized fashion by masked individuals certified in the use of the Goldmann tonometer, Digilab pneumotonometer,and Schiotz tonometer. Possible 5-FU related ocular toxicity will be studied by performing pre- and post-operative complete ocular examinations including standardized measurements of visual acuity, standardized perimetry, and endothelial cell counts. Administrative duties and data analysis will be performed by a Statistical Coordinating Center at the University of Miami. All data will be made available to a Safety and Data Monitoring Committee, which will monitor protocol compliance, evaluate treatment safety and results, and, if indicated, terminate enrollment into any or all strata.